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A role for HEM2 in cadmium tolerance
1Environmental Toxicology Graduate Program, University of California, Riverside 92521, USA.
Journal of Inorganic Biochemistry
|July 9, 1998
Summary
Researchers identified a gene in Candida glabrata crucial for cadmium tolerance. This gene restores cadmium detoxification by enabling the production of glutathione and phytochelatins, essential for heavy metal resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Cadmium (Cd) is a toxic heavy metal.
- Candida glabrata possesses mechanisms for Cd tolerance, involving glutathione and phytochelatins.
- Understanding the genetic basis of Cd tolerance is vital for managing heavy metal exposure.
Purpose of the Study:
- To clone and characterize a gene responsible for cadmium tolerance in Candida glabrata.
- To investigate the role of this gene in the biosynthesis of protective compounds against cadmium toxicity.
Main Methods:
- Construction and screening of a C. glabrata genomic library.
- Transformation of a Cd-sensitive mutant with the genomic library.
- Complementation analysis of a Saccharomyces cerevisiae hem2 mutant.
- Biochemical assays for enzyme activity and metabolite levels.
Main Results:
- A gene restoring Cd tolerance was cloned from C. glabrata.
- The cloned gene encodes a protein homologous to porphobilinogen synthase (HEM2).
- The Cd-sensitive mutant showed reduced porphobilinogen synthase and sulfite reductase activity.
- Cysteine supplementation enhanced Cd tolerance, while hemin chloride and methionine restored it, suggesting a link to heme biosynthesis and transsulfuration.
Conclusions:
- The cloned gene is essential for Cd tolerance in C. glabrata, likely by maintaining the heme biosynthesis pathway.
- Dysfunction in this pathway affects glutathione and phytochelatin production, crucial for detoxifying cadmium.
- Heme availability and the transsulfuration pathway are critical for cadmium detoxification in C. glabrata.